The prevalence of obesity in the United States is increasing, with 35.7% of adults considered obese (BMI≧30) and 68.8% considered overweight (BMI≧25) in 2009-2010. See, for example, Flegal et al. (2012) JAMA 307(5):491-7. Worldwide, over 300 million people are considered obese. Obesity-related diseases, including Type 2 Diabetes Mellitus, hypertension, heart disease, joint disease, and some types of cancer have increased in prevalence as the population has grown heavier.
Prevention of obesity through diet and exercise is of critical importance to control these trends, but once patients become obese, the body's resistance to weight loss can be considerable. Diet and exercise alone may be insufficient to bring about significant weight change in severely obese patients, and both pharmacologic therapy and surgery have proven to be effective as additional aids to weight loss. Prevention and treatment of obesity are areas of high unmet medical need, with few medications currently available for chronic weight loss therapy.
Peptide YY (PYY) belongs to the PP-fold family of peptides together with pancreatic polypeptide and neuropeptide Y, which have a role in controlling appetite. See, for example, Schwartz et al. (2002) Nature: 418(6898):595-7. PYY is secreted as a 36 amino acid, straight chain polypeptide and then cleaved by dipeptidyl peptidase IV to produce PYY(3-36). Fasting and post-prandial concentrations of PYY in morbidly obese individuals after gastric bypass surgery are suggested as playing a role in their dramatic weight loss. See, for example, le Roux (2006) Ann Surg. 243(1):108-14. Peripheral infusion of PYY(3-36) has been shown to increase energy expenditure and fat oxidation rates in obese and lean subjects. See, for example, Batterham et al. (2003) N Engl J Med. 349(10):941-8, and Sloth et al. (2007) Am J Physiol Endocrinol Metab.: 293(2):E604-9. Administration of a PYY(3-36) nasal spray reduced daily caloric intake of obese individuals by 2713 kJ, resulting in a weight loss of 0.6 kg over a six-day study period. See, for example, Gantz et al. (2007) J Clin Endocrinol Metab. 92(5):1754-7. These results demonstrate that obese subjects retain sensitivity to PYY(3-36), in contrast to leptin, where resistance limits its therapeutic usefulness in obesity.
Accordingly, there remains a need in the art for improved PYY compositions for use in the treatment of obesity and obesity-related disorders.